Genomics research in Africa raises a host of ethical issues. An issue that remains understudied is the relation between genomics knowledge and disease stigma. Stigma may be one of the ways in which genomics research could be harmful to individuals and groups of people, but this challenge is not well understood, in Africa or elsewhere. This project seeks to explore the relationship between genomic research and two diseases, namely schizophrenia and rheumatic heart disease, in South Africa. The project employs a mixed methods research approach drawing on the social sciences and psychology to pursue the following aims: Aim 1: to explore the potential impact of genetic attribution of disease causation on internal stigma experienced by patients diagnosed with schizophrenia and rheumatic heart disease in the Western Cape, South Africa. Aim 2: to explore beliefs of individuals representing patient care-givers, family members, healthcare professionals, and members of patient interest groups about the potential impact of genetic attribution of disease causation on structural stigma associated with schizophrenia and rheumatic heart disease in the Western Cape, South Africa. We will examine internal stigma experiences of patients diagnosed with either of these two conditions in Phase 1 of this project. In Phase 1, we will 1) establish a baseline measure of internalized stigma for each participant using the Internalized Stigma of Mental Illness Scale (ISMIS), 2) conduct Focus Group Discussions (FGDs) with a total of 120 amaXhosa patients (60 for each disease) and 3) conduct semi-structured interviews with a 10% randomized sample (n=12) of the patient groups. During the FGDs we will give participants vignettes describing different degrees of genetic causality, and discuss these in the groups. In Phase 2 of the project, we will examine components of more structural stigma in a maximum of 50 semi-structured interviews with patient care-givers, family members, healthcare professionals and members of patient interest groups involved with either schizophrenia or rheumatic heart disease in South Africa. Research will involve amaXhosa participants from two H3Africa genomics research projects currently ongoing in the Western Cape of South Africa. This project will be the first to explicitly investigate the relation between disease stigma and genetics in Africa, and also the first to examine stigma in relation to rheumatic heart disease. Our findings will contribute to an understanding of how concerns about stigma may impact on decisions about the governance of genomic research in Africa.